A frontal pole cDNA library from the rhesus monkey brain was shown to have 6 cDNA clones which are differentially expressed as compared with primary sensory cortices. Three of these clones were identified as mitochondrial DNA encoded genes, cytochrome oxidase (COX) subunits I. II and III, reflecting greater neuropil (synapses and dendrites) and mitochondrial density in association as compared to primary cortices. Such differences in gene expression may be related to selective vulnerability of association than of primary cortical regions in Alzheimer's disease (AD) in humans. Localization of COX activity and mRNA also identified the neurons that are involved in pathway specific and corticocortical connections in monkey and human brain. This distribution of COX mRNA corresponded with the neurons that are selectively vulnerable in Alzheimer's disease. Mouse trisomy 16 (ts16), an animal model for Down syndrome in humans, is a lethal chromosomal abnormalitiy leading to fetal death. However, Ts16 hippocampal tissue was successfully transplanted into brains of normal mouse hosts and survived for periods up to 18 months. The grafts did not demonstrate evidence of Alzheimer's disease neuropathology, suggesting that increased expression of the genes homologous to those on human chromosome 21 is insufficient to cause Alzheimer type neurodegeneration in the mouse.